Genetic Variant ENST00000448879.5:c.-83+27443C>T (chr7-84279764-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448879.5(SEMA3A):c.-83+27443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,072 control chromosomes in the GnomAD database, including 16,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16105 hom., cov: 34)

Consequence

SEMA3A
ENST00000448879.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320

Publications

6 publications found

Variant links:

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	XM_005250110.4 link	c.-83+27443C>T		intron_variant	Intron 3 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.-83+15278C>T		intron_variant	Intron 4 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000448879.5 link	c.-83+27443C>T		intron_variant	Intron 4 of 4	5		ENSP00000402093.1		A0A0C4DG50
SEMA3A	ENST00000424555.5 link	c.-83+27443C>T		intron_variant	Intron 3 of 3	4		ENSP00000404800.1		C9JD25

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67818

AN:

151954

Hom.:

16100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.605

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.446

AC:

67841

AN:

152072

Hom.:

16105

Cov.:

AF XY:

0.444

AC XY:

33016

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.274

AC:

11351

AN:

41500

American (AMR)

AF:

0.435

AC:

6641

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1624

AN:

3472

East Asian (EAS)

AF:

0.605

AC:

3123

AN:

5158

South Asian (SAS)

AF:

0.505

AC:

2435

AN:

4826

European-Finnish (FIN)

AF:

0.433

AC:

4574

AN:

10558

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.538

AC:

36570

AN:

67974

Other (OTH)

AF:

0.472

AC:

997

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1877

3754

5632

7509

9386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.508

Hom.:

9841

Bravo

AF:

0.438

Asia WGS

AF:

0.547

AC:

1900

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.41

PhyloP100

0.032

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over